Particulate agents
A novel means of pharmaceutical delivery for therapy of prophylaxis or to assist surgical or diagnostic operations on the living body is provided by neuronal endocytosis and axonal transport following pharmaceutical administration into vascularized, peripherally innervated tissue, e.g. intramuscular injections of a nerve adhesion molecule in coupled particle comprising a physiologically active substance or a diagnostic marker.
Latest Syngenix Limited Patents:
Claims
1. A method of treating a living human or non-human body to generate a therapeutic or prophylactic treatment or assist diagnostic investigation or surgical treatment thereof, said method comprising administering into a vascularized peripherally innervated tissue site or into other tissue sites innervated by a spinal root a particulate pharmaceutical agent comprising a nerve adhesion moiety serving to promote neuronal endocytosis of said agent and a physiologically active or diagnostic marker moiety for axonal transport from said tissue site.
2. A method of treating a living human or non-human body in need of therapeutic, prophylactic or diagnostic treatment, comprising administering into a vascularized peripherally innervated tissue site or into other tissue sites innervated by a spinal root, a therapeutic, prophylactic or diagnostic composition comprising a nerve adhesion moiety wherein said nerve adhesion moiety is a particulate pharmaceutical agent subject to neuronal endocytosis, said agent further comprising a physiologically active or diagnostic marker moiety for axonal transport following neuronal endocytosis of said agent.
3. A pharmaceutical agent comprising a nerve adhesion molecule coupled to an optionally-coated, particulate, physiologically active or diagnostically marked substance, said substance being one selected from the group consisting of metal oxide, metal sulfide and alloy when said substance is diagnostically marked, wherein said physiologically active or diagnostically marked substance is axonal transport following neuronal endocytosis of said agent, and wherein said particulate have a mean particle size of 10-50 nm.
4. A composition as claimed in claim 4 wherein said particles have a spinel structure.
5. A composition as claimed in claim 5 wherein said particles are superparamagnetic.
6. A composition as claimed in claim 6 wherein said particles incorporate radionuclides.
7. The method, according to claim 1, wherein said particulate pharmaceutical agent is administered in solution.
8. The method, according to claim 1, wherein said particulate pharmaceutical agent comprises a carrier particle coated with a hydrophilic molecule to which said nerve adhesion moiety and said physiologically active or diagnostically marked moiety are bound.
9. The method, according to claim 8, wherein said hydrophilic molecule is dextran.
10. The method, according to claim 8, wherein said carrier particle is a metal oxide.
11. The method, according to claim 2, wherein said particulate pharmaceutical agent is administered in solution.
12. The method, according to claim 2, wherein said particulate pharmaceutical agent comprises a carrier particle coated with a hydrophilic molecule to which said nerve adhesion moiety and said physiologically active or diagnostically marked moiety are bound.
13. The method, according to claim 12, wherein said hydrophilic molecule is dextran.
14. The method, according to claim 12, wherein said carrier particle is a metal oxide.
15. The pharmaceutical agent, according to claim 3, wherein said pharmaceutical agent is administered in solution.
16. The pharmaceutical agent, according to claim 4, wherein said pharmaceutical agent comprises a carrier particle coated with a hydrophilic molecule to which said nerve adhesion moiety and said physiologically active or diagnostically marked moiety are bound.
17. The pharmaceutical agent, according to claim 16, wherein said hydrophilic molecule is dextran.
18. The method, according to claim 16, wherein said carrier particle is a metal oxide.
19. A pharmaceutical agent comprising a nerve-adhesion molecule coupled to an optionally-coated, particulate, physiologically active or diagnostically marked substance, said substance being one selected from the group consisting or metal oxide, metal sulphide and alloy when said substance is diagnostically marked, wherein said physiologically active or diagnostically marked substance is for axonal transport following neuronal endocytosis of said agent.
4430320 | February 7, 1984 | Shigematsu et al. |
4452773 | June 5, 1984 | Molday |
4479940 | October 30, 1984 | Bizzini |
4552145 | November 12, 1985 | Riley et al. |
4594336 | June 10, 1986 | Bizzini |
4690130 | September 1, 1987 | Mirell |
4752567 | June 21, 1988 | De Brabander et al. |
4813399 | March 21, 1989 | Gordon |
4827945 | May 9, 1989 | Groman et al. |
4849210 | July 18, 1989 | Widder |
4863715 | September 5, 1989 | Jacobsen et al. |
5019369 | May 28, 1991 | Presant et al. |
5043101 | August 27, 1991 | Gordon |
5077035 | December 31, 1991 | Wieland et al. |
5169933 | December 8, 1992 | Anderson et al. |
5248772 | September 28, 1993 | Siiman et al. |
5382468 | January 17, 1995 | Chagnon et al. |
5424288 | June 13, 1995 | Order |
5492814 | February 20, 1996 | Weissleder |
5554498 | September 10, 1996 | Filler et al. |
0455093 | November 1991 | EPX |
8601112 | February 1986 | WOX |
8800060 | January 1988 | WOX |
8909625 | October 1989 | WOX |
9001295 | February 1990 | WOX |
9101144 | February 1991 | WOX |
9104014 | April 1991 | WOX |
- Gallagher, J.E., G. George, A.R. Brody (1987) "Sialic acid mediates the initial binding of positively charged inorganic particles to alveolar macrophage membranes" Am. Rev. Respir. Dis. 135(6):1345-1352 (abstract only). Menetrey, D. (1985) "Retrograde tracing of neural pathways with a protein-gold complex" Histochemistry 83(5):391-395 (abstract only).
Type: Grant
Filed: Jun 7, 1995
Date of Patent: Sep 7, 1999
Assignee: Syngenix Limited
Inventor: Aaron Gershon Filler (Seattle, WA)
Primary Examiner: Jose G. Dees
Assistant Examiner: Dameron Jones
Law Firm: Saliwanchik, Lloyd & Saliwanchik
Application Number: 8/473,697
International Classification: A61K 5100; A61M 3614;